There are numerous applications in which implantable hydrogels or compositions are implanted into mammals for purposes of drug delivery, and tissue regeneration. Hydrogels are generally defined as polymeric materials that swell in water and other fluids, absorbing the fluid within the polymer network without dissolving. Hydrophilic hydrogels have a large amount of water content at equilibrium, and good biocompatibility.
Hydrogel matrices have been developed to promote tissue regeneration after injury, and to locally deliver drugs. In tissue regeneration, the chemical makeup and structural alignment of the gel can influence the way cells attach and move through it, and much work is being done to rationally design gels as synthetic tissue analogues to support cell regrowth after injury [15-19]. For example, synthetic hyaluronic acid gels have been used to guide neurons to the site of a spinal cord injury, with the aim of completely regaining spinal cord function [18, 20]. Many synthetic hydrogels are structurally similar to biological hydrogels, but have a simplified, well-controlled structure. These constructs are important physical models used to understand the structure and function of the extracellular matrix. The gel structures have been sensitized to local enzymatic degradation, temperature, and cell growth [16, 17, 21-25]. This is important in polymer gels with controlled-release properties, which are designed to deliver drugs upon changes in the local microenvironment [26-28].
Upon implantation of the hydrogel device, interaction of these hydrogels with the surrounding tissue is complex, making it important to monitor the molecular structure of the gels once implanted. Molecular imaging methods have been developed to provide real-time, in vivo spatial maps of molecules. Several molecular imaging modalities are now widely used, and show promise for detecting molecules in humans noninvasively in the clinic. Optical imaging, in particular, has been successful in highly sensitive detection of molecules, as demonstrated by the routine use of fluorescent reporter proteins in cellular and animal experiments, and in vivo confocal microscopy is used to study cell and vascular function in humans during surgery [29-31]. However, optical imaging suffers from a limited penetration of light, making imaging at depths of over a few centimeters difficult. Other technologies, such as PET, CT, and SPECT, offer whole-body penetration, but have limited resolution and rely on ionizing radiation for contrast [32]. Radio-opaque polymers are used to detect gels with x-ray and CT [1,9], and fluorescent conjugates are commercially available for labeling gel molecules for optical imaging [33, 34]. Nevertheless, while these techniques hold some promise, none allows for a non-invasive techniques allows for noninvasive, three-dimensional imaging of gel structure after implantation in animals and humans. Thus, once the gel is implanted, there is currently no method of determining whether the payload in the gel has been delivered or whether the gel has attracted the appropriate cells for regeneration.
Thus, there remains a need for a hydrogel composition that can report on its physical status within the body in a noninvasive, three dimensional manner.